Methods for regenerating alveolar bone damaged by periodontal diseases include a method in which the bone defect is filled with an autograft. Another method uses either a human or animal bone, the immunogenicity of which was removed, as an artificial bone replacement material, or a commercially available hydroxyapatite.
In recent years, there has been an active attempt to introduce an artificial membrane into damaged periodontal tissue in order to promote the healing of the damaged tissue, induce the restoration of complete periodontal tissue, improve the result of bone grafting and induce the production of new periodontal bone. The membrane that is used in this technology isolates and blocks the damaged site from the surrounding connective tissue to produce new periodontal bone and periodontal ligament tissue so that the regeneration of periodontal tissue can smoothly occur. In other words, the damaged site is blocked from the surrounding environment by the membrane so that gingival fibroblasts cannot invade the damaged site, and cells in the tissue, which has the ability to regenerate bone and a periodontal ligament, can regenerate new periodontal tissue without interference.
In addition, because bone damage caused by various diseases or trauma has an important influence on human movement, a treatment is required, which can maintain the continuity of the skeletal system and mechanically support the body. Currently, bone regeneration or bone replacement treatments are frequently being performed, but have many problems.
Previously, non-degradable materials such as polytetrafluoroethylene, cellulose acetate, silicone rubber and polyurethane were used as the membrane. However, a membrane made of a non-degradable material has low biocompatibility, and for this reason, secondary surgery is required to remove the membrane after production of periodontal bone, and in this procedure, unnecessary inflammation or tissue necrosis can occur.
Recently, studies on the use of biodegradable polymers such as aliphatic polyester or collagen have been reported. It has also been reported that the use of a biodegradable membrane eliminates the need for secondary surgery for removing the membrane and has no significant difference from the use of a membrane made of a non-degradable material in tissue regeneration. However, in the case of a membrane made of aliphatic polyester, acidic degradation products can cause an inflammatory reaction in the grafted site. Thus, there was a report on the use of a membrane made of collagen, which forms a great part of bone tissue protein, in clinical trials.
In the prior art, Korean Patent Laid-Open Publication No. 2003-002224 discloses a membrane for inducing tissue regeneration, which is prepared from the natural polymer chitosan and a synthetic biodegradable polymer. Herein, the membrane is prepared by applying a biodegradable polymer solution to a nonwoven fabric made of chitosan to form a polymer film, and then laminating the nonwoven fabric made of chitosan on the polymer film, and thus there is a shortcoming in that the preparation process is complex. In addition, Korean Registration No. 0564366 discloses a membrane for tissue regeneration, which comprises a nonwoven nanofiber fabric, has a specific strength, biocompatibility and biodegradability, includes micropores whose pore size can be easily controlled, and can be prepared from a mixture of a natural polymer and a synthetic polymer by a simple process. However, such a conventional membrane for tissue regeneration has a drawback in that, because a tissue growth factor is physically mixed with this polymer membrane or scaffold, it is immediately released after being applied, making it difficult to maintain the effective concentration thereof during a treatment period.
In addition, there was a study on introducing tissue growth factors or extracellular matrix-derived substances into a membrane in order to improve the tissue regeneration ability of the membrane. Because these growth factors and substances are proteins, they should maintain their three-dimensional structure in order to maintain their activity. However, there is a shortcoming in that most of these growth factors and extracellular matrix-derived substances are susceptible to temperature, and thus are likely to be unstable in vivo.
Thus, in order to obtain a desired therapeutic effect, tissue growth factors and extracellular matrix-derived substances should be administered at high doses, but in this case, side effects can occur. In order to overcome this problem, an attempt was made to introduce tissue growth factors inside or the surface of a membrane. However, if a tissue growth factor is physically adsorbed onto a membrane, the bonding thereof cannot be maintained for a long period of time, whereas if a tissue growth factor is covalently bonded to a membrane, the bonding thereof can be stably maintained for a long period of time using a crosslinking agent. However, in this case, there is a problem in that the crosslinking agent can result in the deformation of the three-dimensional structure of the tissue growth factor, resulting in a decrease in the activity of the tissue growth factor.
Accordingly, the present inventors have made extensive efforts to prepare a collagen membrane having antibacterial activity on the surface thereof, and as a result, have found that, when a fusion peptide consisting of an antibacterial peptide linked to a peptide having the ability to bind to collagen is bound to a collagen membrane, it can impart surface antibacterial activity to the membrane, thereby completing the present invention.